rs1553267067

Variant names:

• chr1-210021084-G-A
• rs1553267067
• NM_001146262.4:c.272G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001146262.4(SYT14):​c.272G>A​(p.Ser91Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SYT14 NM_001146262.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.12
• Publications: 0 publications found

Genes affected

SYT14 (HGNC:23143): (synaptotagmin 14) This gene is a member of the synaptotagmin gene family and encodes a protein similar to other family members that mediate membrane trafficking in synaptic transmission. The encoded protein is a calcium-independent synaptotagmin. Mutations in this gene are a cause of autosomal recessive spinocerebellar ataxia-11 (SCAR11), and a t(1;3) translocation of this gene has been associated with neurodevelopmental abnormalities. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 4. [provided by RefSeq, Dec 2011]

SYT14 Gene-Disease associations (from GenCC):

• autosomal recessive spinocerebellar ataxia 11

  Inheritance: Unknown, AR Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31186926).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001146262.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYT14	NM_001146262.4	MANE Select	c.272G>A	p.Ser91Asn	missense	Exon 4 of 9	NP_001139734.1	Q8NB59-6
	SYT14	NM_001397544.1		c.1142G>A	p.Ser381Asn	missense	Exon 5 of 9	NP_001384473.1	A0A8V8TN09
	SYT14	NM_001397545.1		c.1142G>A	p.Ser381Asn	missense	Exon 6 of 10	NP_001384474.1	A0A8V8TN09

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYT14	ENST00000367019.6	TSL:1 MANE Select	c.272G>A	p.Ser91Asn	missense	Exon 4 of 9	ENSP00000355986.1	Q8NB59-6
	SYT14	ENST00000472886.5	TSL:1	c.272G>A	p.Ser91Asn	missense	Exon 4 of 8	ENSP00000418901.1	Q8NB59-1
	SYT14	ENST00000367015.5	TSL:1	c.158G>A	p.Ser53Asn	missense	Exon 4 of 8	ENSP00000355982.1	Q8NB59-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461712 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727162

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111872

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.64
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.063	T
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		8.1
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.15
Sift	Benign	0.061	T
Sift4G	Benign	0.083	T
Polyphen		0.99	D
Vest4		0.59
MutPred		0.28		Loss of phosphorylation at S91 (P = 0.0073)
MVP		0.39
ClinPred		0.96	D
GERP RS		5.4
PromoterAI		0.019	Neutral
Varity_R		0.41
gMVP		0.61
Mutation Taster		=31/69	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1553267067; hg19: chr1-210194429;